The proposed research will investigate the mechanism of action which membrane acting drugs may have on excitable cell membrane structure and function. The parameters of membrane function to be examined will be membrane resistance, membrane potential, specific ionic permeabilities, and the excitable properties. In nerve and muscle, the membrane components which regulate ionic permeability will be investigated and the nature of interaction of drugs with these components determined. This study will initially investigate the mode of action of neuropoisons and local anesthetics. Further research will examine modes of action for the barbiturates, the narcotic analgesics, and other membrane interacting agents. The changes in membrane structure and function which might occur with drug dependency and addiction will also be explored. This research will contribute to an understanding of the mode of action of drugs at the molecular level.